What The Doctor Ordered: Building New Body Parts

This is SCIENCE FRIDAY. I'm Ira Flatow. Over 115,000 Americans are currently waiting for an organ transplant, and most of them are in need of a kidney. Now, what if we could just create a kidney for them in the laboratory? One of my next guests has experimented with printing out organs using an inkjet printer, but instead of ink, he uses cells.

He's already produced a prototype kidney with that method, and he's grown working, transplantable bladders in his laboratory also. My other guest worked with a veteran of the Afghanistan war whose left thigh was blown off by a roadside bomb seven years ago, and the Marine was considering an amputation, but today he's walking and even running after growing back that missing muscle.

Why doesn't the body make these repairs automatically? Babies in the womb build their organs and bones and flesh from scratch. So why can't adults do the same or rebuild ones that are damaged? As scientists learn more about how the body builds itself, the sci-fi ideas are on their way towards becoming medical reality.

So building and repairing body parts is what we're going to be talking about this hour. Our number is 1-800-989-8255, 1-800-989-TALK. You can also tweet us @scifri and go to our website or our Facebook at scifri. Let me introduce my guests.

Dr. Anthony Atala is director of the Institute for Regenerative Medicine at Wake Forest University in Winston-Salem, North Carolina. He joins us on campus. Welcome to SCIENCE FRIDAY, Dr. Atala.

DR. ANTHONY ATALA: Good to be with you today.

FLATOW: Thank you. Dr. Stephen Badylak is deputy director of the McGowan Institute for Regenerative Medicine at University of Pittsburgh in Pennsylvania. He joins us by phone. Welcome to SCIENCE FRIDAY, Dr. Badylak.

DR. STEPHEN BADYLAK: Thank you, happy to be here.

FLATOW: Let me start with you, and let's talk about this study you did to rebuild the muscle in that soldier. Tell us how that works.

BADYLAK: Well, as you indicated in your lead-in, we innately have the ability to grow tissues and organs and do everything - not quite from scratch, I would argue with that. There's a starting cell. But the - we lose that ability with time and age as we mature, and instead of re-growing tissues and organs, we learn how to develop an inflammatory reaction and then fill in the missing tissue with scar instead.

So there's a lot of hype about stem cell therapy and other types of therapy that can hopefully re-grow this type of tissue, but what we've done is identify a biologic material that takes advantage of what the body would like to do by creating an environment in which it recruits the body's own stem cells to the site, sort of like a homing device.

And then by providing a friendly environment for these cells, they get the message that they should rebuild tissue rather than replace it with scar.

FLATOW: So you implant something in that spot that you want to be rebuilt?

BADYLAK: Right, we don't use cells, we use it's called extracellular matrix. It's a biologic scaffold material. It's Mother Nature's version of a reservoir for information that tells the body's own cells what to do.

FLATOW: And so then the body recognizes that, and it tells the body to collect its own stem cells and start to build muscle tissue?

BADYLAK: That's one of the things - the ways that it works, and we're still trying to figure out all of the different mechanisms that Mother Nature has built into our matrix and other parts of our body that direct these stem cells.

FLATOW: And how successful have you been in these experiments?

BADYLAK: Well, the soldier that was featured in this article in the New York Times is one of 80 that we're going to be implanting in this clinical trial. We've implanted six patients now, and all of them basically have been very successful, with results similar to the Marine that the story was about.

These soldiers - or civilians, it doesn't have to be a soldier. It can be anybody who's lost their significant piece of muscle, too much for the surgeon to be able to sew together because there's nothing left. So this study, which is funded by the Office of the Secretary of Defense and the Manufacturing Technology Program for the (unintelligible) director, basically the Defense Department is funding this totally.

So patients that are potentially eligible can enter this study fully paid, you know, by our tax dollars to take advantage of this technology.

FLATOW: So you're actually trying to recruit people now for your study?

BADYLAK: We sure are.

FLATOW: How do they sign up? We have actually on our website a link to go to your study, but you're publicly announcing you want people for your study.

BADYLAK: That's exactly right. We've got - we've done six of the 80 so far, and everything so far looks like it's working pretty well, and we, you know, we're very careful about the patients that we screen, very - we want to be sure that we have the opportunity to do some good for these patients.

FLATOW: How old can the injury be? Does it have to be a fresh injury?

BADYLAK: Well, as a matter of fact, we want the injuries to be longer than six months from the time of injury because after we've intervened, we want to avoid the criticism to say well, how do you know they wouldn't have gotten better anyway? So like the Marine, who was seven years out and had been through multiple, multiple surgeries, everything else had pretty much failed.

So these - any patient who's had an injury older than six months of age - six months old is eligible for this study.

FLATOW: Wow. And as I say, you can find - if you're interested and want to become part of the study, go to our website at sciencefriday.com, and we'll have a link there for reaching Dr. Badylak. Dr. Atala, let's talk about this printout kidney. How do you print an organ?

ATALA: Well, you know, not unlike how you print anything with your own printer on your desk, actually. You know, we're using very similar technologies, such as you would see in your desktop inkjet printer, but instead of using ink, we use cells. And we're printing just one layer at a time so that the structures actually come out in a three-dimensional manner that resembles the tissue or the organ we're trying to create.

FLATOW: And so how does the kidney form?

ATALA: So, you know, the kidney is actually quite a complex organ, and of course we've actually created already miniature structures like the kidney that we've been able to implant experimentally, in experimental models, showing that they do produce dilute urine. And they do have the properties of the kidney tissue.

And these are small structures. They're small structures, and what we're really trying to do with the printing technology is really scaling it up: How can we actually make these organs larger so they can be used in patients, and also how can we make these organs in a more precise manner? Because, you know, at the current time, really the technology involves creating organs one tissue - one layer at a time and kind of handmade, if you will.

So the printing technology allows us to expand that and to make many more organs at the same time.

FLATOW: So the difference between the two researches is that in one, Dr. Badylak, you're staying in the body and allowing the body to regenerate its own tissue and perhaps organs, and Dr. Atala, you're taking it out of the body, into a laboratory, making an organ and reinserting it back in. Would that sum it up correctly?

ATALA: Yeah, there are several strategies, actually, you know, that we're pursuing, and we also are - we believe in both strategies, of course, and we are pursuing similar strategies where you can actually allow the body to regenerate and in terms of larger structures, more complex organs, and to allow the production to happen outside the body, when you need more complex tissues.

BADYLAK: Ira, I think your characterization is pretty accurate, as Tony was saying. There's - it's not a one-solution-fits-all scenario. One of the nice things about regenerative medicine is that we can come at it from multiple directions and solve these problems using the tools that are available.

You know, with our approach in this particular study, we happen to utilize what I think is the absolute best bioreactor, which is, you know, the human body because the bioreactors that we make artificially are based upon what we know, you know, and there's just some - in some instances, we just don't know all of the different variables that go into making cells do certain things or what we would really like them to do.

So whenever we can, we use the body as the bioreactor, and by - if you can get away with not using cells, like we seem to be able to do here with this muscle tissue, that simplifies things a lot. It decreases the cost of the therapy, it decreases the complexity, the type of regulatory approvals that might be needed through the FDA and so forth.

So - but as I said, one size doesn't fit all, and yeah...

FLATOW: These scaffolds you use, these extracellular materials, what it is exactly, and how does it send messages to the body? Do you know how that works, hey, come here and build something?

BADYLAK: Well, you know, we've been spending a lot of years trying to figure that out and we're getting the answers sort of one at a time. And it's really - that's, you know, for the science nerds like myself, we - it's pretty cool what Mother Nature has built into the system.

In this extracellular matrix, which is basically the glue that holds the cells together and the different tissues, there's hidden signals. And by isolating the matrix, when you put it in the body, the body begins to break it down, and it releases these signals. And these signals do things like they can fight off bacteria in some cases. They can recruit cells in cases. They can moderate the inflammatory response and change it from something that's destructive to something that's constructive.

So it's really just amazing how this information's there, and we're just trying to take advantage of what Mother Nature has provided for us.

FLATOW: Do both - do you actually marvel at these advances along with the rest of us who read about them and talk to you about them that my goodness, this actually works?

(LAUGHTER)

BADYLAK: Well, I don't know about Tony, but I do all the time. I get - I think I've got the best job in the world. I love coming in because you're just, you know, getting a chance to see these things and figure them out and have fun at it and at the same time benefit people, you know, with these types of clinical trials.

ATALA: Absolutely. You know, the best thing about these technologies is finally getting to see these technologies get into patients, you know, and actually seeing patients benefitting from these technologies.

FLATOW: Where's the sky on this? What's the limit of organs that you cannot or can do? And what successes have you all had, which organs? Tony, want to go first?

ATALA: Sure. You know, I think that there's - you know, there's a certain level of complexity, of course, in terms of organs and how we approach them. You know, you have flat structures such as skin, which are definitely the simplest, because they're really mostly one cell type, and architecturally they're just flat structures as opposed to tubular structures like blood vessels, which are more complex because you have two different cell types, it's tubular.

And then you have hollow, not tubular, organs like the stomach or the bladder, which are a little bit more complex. The cells are more complex. The structure is more complex. And finally you have the solid organs like the heart, the kidney, the liver, which are definitely the most complex.

So up to this point we've, you know, been lucky to have seen the achievement of the first three types of tissues that have been already placed in patients.

FLATOW: All right, let me - I'm going to have to interrupt here because we have to take a break, but we'll come back and cover the rest of those organs and what the future holds. So stay with us, please. We'll be right back after this break.

And when I interrupted, we were talking about what possibilities there are for building the organisms outside of the body, and you were going up in order of difficulty. And where do we stand now in that order? What can we do? What are we looking to do?

ATALA: Yeah, so basically right now if we look at the field, you know, you can see the replacement of the first three types of tissues: flat tissues like skin; tubular structures; hollow, non-tubular organs. But really we have not yet been able to achieve the full regeneration of solid organs. And that's really where a lot of the challenges are today.

But we certainly have seen the first three types already in humans.

FLATOW: Dr. Atala, which, if any, of these regenerative treatments are actually routine today? In other words, if you went to a hospital, what could they do for you now?

ATALA: So today if you walked into a hospital and you had a damaged knee or a problem in your knee, you can actually get cells from your own knee that they could process and they could put back in to repair the knee for specific injuries.

And the same thing for skin, actually. Patients with burns or other problems that may involve the skin, you can actually have engineered skin that gets used to repair those - to repair those injuries and treat those patients.

FLATOW: It's really spray-on skin?

ATALA: At the current time, the spray-on skin is actually being used commercially now in Europe. It is now in clinical trials here in the U.S., and there are about 10 centers currently involved in a clinical trial with spray-on skin. But the hope is to also have that available here in the U.S. in the near future.

FLATOW: Stephen Badylak, you also looked at ways to just inject a gel that spurs the body to repair itself.

BADYLAK: Well, the - yes, what we're trying to do is take advantage of the signals we were talking about that exist within this matrix that do these, you know, kind of neat things. And then in - the whole idea is to put these types of signals in the location that's needed as simply as possible. You know, in the applications in this clinical trial for skeletal muscle, for example, it's a surgical procedure where the site is opened surgically, obviously under anesthesia, scar tissue is removed, and we place a scaffold, and then we rebuild the tissue with, you know, the protocol post-surgery.

BADYLAK: But just imagine if you could, for example, take advantage of these signals by putting them into a heart after a heart attack without having to open it up. You know, we already know how to put catheters there and get stints and other things in place. Well, maybe while we have a catheter there we could just inject the same signals in the form of a gel (unintelligible).

BADYLAK: And so we're looking at applications like that. We know we can make the gel. We know we can deliver the signals. The question now is, what applications are going to respond favorably to that form of it, the idea being treat the patient as quickly and as easily as possible, minimize time in the hospital and accelerate the recovery.

FLATOW: What about neurons or brain cells? Are they on the horizon?

BADYLAK: They sure are. The question is whether or not we'll - you know, how much success we'll have because that - in the organ hierarchy that Dr. Atala was describing, you know, you probably - probably central nervous system tissue is at the very top. It's obviously very complex, but the idea would be that patients - right now, you know, patients that have a stroke - there's very few people who think we could re-create functional brain tissue.

BADYLAK: Instead, we take these patients and we try to just teach them how to live with their deficit. There's a group of us in regenerative medicine who say, you know, that's not acceptable. We can do better than that. So we're taking these same principles - cell-based approaches and scaffold-based approaches, and seeing - you know, we've now identified that there indeed is a stem cell population in the brain and in the spinal cord.

BADYLAK: Let's see whether we can mobilize those cells and have them do something good. One way to look at it is the bar's pretty low, right? I mean even if we could make a 25 percent improvement in these patients, we could change their quality of life. So you know, our goals have got to be realistic and yet based on things that we learn in all of these other applications.

FLATOW: Is there any possibility - I talked about this before, about if a salamander can regenerate a limb, why can't we? Why can't we? And is that too much pie in the sky to talk about?

BADYLAK: Well, there obviously are limits because we're such different species. But, you know, we all start out pretty much the same in the way we develop in the womb and create sophisticated body systems and so forth. We lose that regenerative ability, but, you know, we traded it off for some other things that are pretty good.

BADYLAK: So there are studies - and I think this is where regenerative medicine really can do some good, it brings together different sciences - by working with people and scientists in developmental biology who understand, you know, which genes are turned on and which ones are turned off in a regenerating species like a salamander, and then comparing the same injury at the same time point in non-regenerating species like man, you know, we can identify which are the key genes, and what turns them on, what turns them off. So I think, you know, somewhere in the future we're going to be better at controlling gene expression and actually be doing at least some version of that.

FLATOW: And Dr. Atala, speaking of somewhere in the future, when I hear researchers like you and Dr. Badylak talk about the future, you're not talking about decades here, are you? You're talking about years instead of decades for getting results.

ATALA: Yeah, certainly that's the case now, you know, but still, there's still challenges ahead. You know, we still have challenges in terms of the cost of the technologies and how to make sure they get produced in a manner that's not just one at a time, but we can really scale up the production of these organs.

And so really the goal of the field right now is really - one of the major goals is to make sure that we can increase the number of tissues that we can offer patients and also to increase the number of indications that can benefit from these technologies.

FLATOW: Would you agree?

BADYLAK: Well, I do. I think there's another challenge. In some cases, and I think this is one that - it's advancing so rapidly that it's hard for regulatory agencies like the Food and Drug Administration to keep up. You know, they're being presented with new devices and methods for treating patients that they never have before. And so there's not a template for how they approve them. And that tends to slow things down sometimes.

BADYLAK: So in addition to the cost, there's the regulatory approval. So in these cases I think the science is actually outpacing the ability of the system to keep up with it. And of course the patients are the ones who have to suffer because they know, and they hear programs like this, and they think why can't I take advantage of that.

BADYLAK: So you know, it's a whole different part of solving this problem.

FLATOW: So you're moving so fast that getting the regulatory process to keep up with you, to try new things, is sort of like molasses here.

BADYLAK: Right, I mean approving a drug for use, there's a template for doing that, or a medical device. But when you have something that you have a combination of cells and biologic scaffolds that come from, you know, a different species, that - there's no template for that. And so the regulatory agencies have to say OK, what makes sense to do.

FLATOW: So where do you go with your research now? What's your next goal?

BADYLAK: Tony? Go ahead, Tony.

ATALA: Oh sure, thank you, Steve. I think it's clear that now - that these technologies are definitely technologies that can benefit patients. I mean, that was a question we had just two decades ago. There was - some of these technologies that were really considered science fiction, can they really do what we want them to do.

And so now we do have a history of patients receiving these technologies. We have patients now walking around with engineered organs, have been out(ph) for more than 10 years and doing well. So we know that the potential is there. The challenge for us is how do we actually make sure that we can keep delivering technologies that can improve patients' lives.

And I think that's really a challenge that's been mentioned for many reasons. And it's not just, you know, the cost and the regulatory challenges that we were talking about but also the fact that at the end it really will depend mostly on how patients present. All these technologies are developing, but at the end of the day there is no perfect cell, there is no perfect technology.

It really will depend on how the patient presents. For example, a person who has end-stage heart disease or failure, the last thing you want to do is to go in and take a biopsy or a piece of tissue from their own heart. I mean the procedure itself would harm the patient. So even though we can grow heart cells from the patient, you may not want to do that in that patient with end-stage disease.

You maybe want - you could do it when the patient's starting to develop the heart disease but not at the end. The other thing I want to mention is that the goal of the technology today is to treat patients who already have end-stage disease.

BADYLAK: The other thing I want to mention is that the goal of the technology today is to treat patients who already have end-stage disease. The best hope for the field, is really to start identifying and treating patients early on and to use these technologies before they get to that end point, where now they have this organ failure going on. You want to catch these patients early so you can prevent them from getting there in the first place.

FLATOW: All right, gentlemen. I want to thank you both for taking time to be with us today. Fascinating research. And we will, with your cooperation, keep track of what you're working on. Have a - thanks again for joining us. Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University in Winston-Salem, North Carolina. Dr. Stephen Badylak is deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh in Pennsylvania. Have a good weekend, gentlemen. Thanks again.